ADEPT® (4% ICODEXTRIN) ADHESION REDUCTION SOLUTION

PMIA Number: P050011

Proposed Product Labelling

Page 1 of 19

ADEPT? (4%ICODEXTRIN) ADHESION REDUCTION SOLUTION

INFORMATION FOR PRESCRIBERS

CAUTION: FEDERAL LAW RESTRICTS THIS DEVICE TO SALE BY OR ON THE ORDER OF A PHYSICIAN.

CAUTION: DO NOT USE UNLESS SOLUTION IS CLEAR AND CONTAINER IS UNDAMAGED.

CAUTION: ADEPT? is for direct intraperitoneal administration only. NOT FOR INTRAVENOUS (IV) ADMINISTRATION.

I. DEVICE DESCRIPTION AND MECHANISM OF ACTION

ADEPT * (4% Icodextrin) Adhesion Reduction Solution is a single use, sterile, clear, colorless-to-pale yellow fluid for intraperitoneal administration containing icodextrin at a concentration of4% w/v in an electrolyte solution. Icodextrin is a corn starch-derived, water-soluble branched glucose polymer linked by alpha (I1-4) and less than I0% alpha ( 1-6) gILucosidic bonds with a weight-average molecular weight between 13,000 and 19.000 Daltons and a numnber-average molecular weight between 5,000 and 6.500 Daltons. The representative structural formula of icodextrin is:

Figure I: Structural Formula of lcodextrin

H-

OH

H

H_

O

OH

OH

H 0

0

-- OH

OH OH~~~~~~~~

PMA Number: P050011

Proposed Product Labelling

Page 2 of 19

Each I liter of ADEPT?'contains: Icodextrin Sodium Chloride Sodium Lactate Calcium Chloride Magnesium Chloride

40g 5.4g; 4.5 g 257mg

51mg

Theoretical osmolarity 278 milliosmoles per liter

Ionic composition (approximately) per liter:

Sodium

133 mmnol

Calcium

I .75 mmol

Magnesium

0.25 mmol

Chloride

96 mmol

Lactate

40 mmol

ADEPT" is packaged in flexible polyvinyichloride bags containing I L or 1.5 L of Solution. When stored at temperatures below 300C ADEPT?~ has a shelf life of 24

months. A DEPT?~should not be refrigerated or firozen.

MIECHIANISM OF ACTION AND CLEARANCE

Icodextrin, as an alpha (1-4)-linked glucose polymer, is similar in structure to carbohydrates which occur physiologically, e.g. glycogen. When administered intraperitoneally as a 4% solution, icodextrin functions as a colloid osmotic agent. This colloidal osmotic action of icodextrin allows the retention of a reservoir of fluid withinl the peritoneal cavity for 3-4 days.'

AI)Ll'1l, is believed to perform its function through a physical effect by providing, a temporary separation of'peritoneal surfaces by hydroflotation as a result of maintaining a fluid reservoir. This minimizes tissue apposition during the critical period of' fibrin formation and mesothelial regeneration following surgery, thereby providing a barrier to adhesion formation.

Pharmacokinctics of Icodextrin Absorption

Absorption of icodextrin from the peritonea[ cavity follows zero-order kinetics, consistent with convective transport via the lymphatic pathways. Studies ill patients Undergoing continuous ambulatory peritoneal dialysis (CAPD) indicate that a median of 40% of the instilled icodextrin was absorbed from the peritoneal solution during a 12 h1our dw~ell. 2

52)

PMA Number: P050011

Proposed Product Labelling

Page 3 of 19

Metabolism and Elimination

When given intraperitoneally, the icodextrin polymer is not metabolized significantly in the peritoneal cavity but is slowly transferred into the systemic circulation by peritoneal lymphatic drainage. In the systemic circulation icodextrin is rapidly metabolized by alpha-amylase to lower molecular weight oligosaccharides, which along with icodextrin, are eliminated by renal excretion. The rate of clearance of icodextrin from the systemic circulation has been estimated to be equal to glomnerular filtration rate.

II. INDICATION, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS

INDICATION FOR USE

ADEPTZ' Adhesion Reduction Solution is indicated for use intraperitoneally as an adjunct to good surgical technique for the reduction of post-surgical adhesions in patients undergoing gynecological laparoscopic adhesiolysis.

CONTRAINDICATIONS

ADEPT" is contraindicated:

* In patients with known or Suspected allergy to cornstarch based polymers e.g., icodextrin. or with mnaltose or isornaltose intolerance, or with glycog-en storage disease.

* Ii the presence of frank infection (e.g. peritonitis) in the abdormino-pelvic cavity.

* In procedures with laparotomy incision. Serious post-operative Wound complications including dehiscence and Cutaneous fistula formation have been reported from clinical experience outside the US when ADEPT?~was used in surgical cases with laparotomy incision.

* In procedures involving bowel resection or repair, or appendectomy. Anastornotic failure, ileus and peritonitis following procedures involving bowel resection and instillation of ADEPT? have been reported from clinical experience Outside of the US.

,35

PMA Number: P050011

Proposed Product Labelling

Page 4 of 19

WARNINGS

Thereave ben rare reports of seieperitonitis following the use -of icodextrin. The differential diagnosis of abdo-ilno-pelvic pain following instillation of ADEPT' should include peritoneal cavity infection, perforated bowel or other viscous, intraperitoneal bleeding, and other life threatening post-operative complications in addition to sterile peritonitis.

*Leaking ADEPT"' fluid through laparoscopic prt sites post-operatively is associated with wound complications such as subcutaneous fluid collection, skin separation and infection. Meticulous closure ~of fascia may help reduce wound complications related to fluid extravasation following gynec ologic laparoscopy surgery.

*There have been rare reports of hypersensitivity reactions ih patients treated with ADEPT?~. Anaphylaxis has been reported in a few patients.

* There are rare reports of pulmonary edema, pulmonary effusion and arrhythmia fromn clinical experience with ADEPT? outside of the US. These cases tended to occur in elderly or otherwise debilitated patients (e.g. cancer patients). The potential benefit of ADEPT? for adhesion prevention should be carefully weighed against the risk of serious complications in patients with serious co-morbidities.

* Foreign body reactions may occur with ADEPT?, as with any implanted material.

PRECAUTIONS

* ADEPT?"is for direct intraperitoneal administration only. NOT for intravenous (IV) administration.

*ADEPT? is not indicated asadlvery system for intrprtna rg uha antibiotics and chemnotherapeutic agents.

? The effectiveness of ADEPT?e has not been established for longer term clinical outcomes following gynecological surgery, e.g. pregnancy and pain.

* Self-limnited vulvar swelling is a kn-own'side-effect of instilling large volumes of fluid into the abdornino-pelvic cavity. Most cases resolve within one week of surgery. When swelling is associated with urinary retention, catheterization may be necessary,.

* Maltose metabolites of icodextrin 'may interfere with blood glucose measurement in diabetic patients who use rapid blood glucose systems that are not glucose specifc

PMA Number; P050011

Proposed Product Labelling

Page 5 of 19

The safety and effectiveness of ADEPT?'have not been evaluated:

* in patients less than 18 years of age; * in pregnancy; ? when volume left in peritoneal cavity exceeds I L; * in patients with abnormal liver and/or renal function; or * in cases where there is a breach in the vaginal epithelium;

II 1.ADVERSE EVENTS

Postmarketintz Passive Surveillance Outside of US

ADEPT? Adhesion Reduction Solution was approved for use in Europe in October 1999. A Europe-wide multicenter registry for evaluating clinical experience using ADEPTO was launched in 2000. The ARIEL registry was intended to capture the experience of surgeons using ADEPT" in both general and gynecological surgery. Data were collected between September 2000 and December 2003.

A total of 4620 patients were enrolled in the ARIEL registry. Of these, 2882 were gynecologgy patients (72% laparoscopy) and 1738 were general surgery patients (85% laparotomny). Adverse events were reported in 7.5% gynecological laparoscopy and 13.9% gynecological laparotomy patients compared with 16.7% general surgery laparoscopy and 30.60o general Surgery laparotorny patients.3 ' Table I summarizes key events. These events are presented regardless of the reporting surgeon's causality assessment.

 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download